Cytokines are proteins that regulate the body's immune response to infection. An overproduction of cytokines causes the body's immune system to go into overdrive and attack itself. This can cause extensive inflammation and tissue damage.

Cytokine storms are thought to be responsible for many deaths in the 1918 flu pandemic, as well as in more recent outbreaks of bird and swine flu.

Researchers previously believed these storms were initiated by virus-infected cells lining the lungs and nasal passages.

But the study findings, reported in the journal Cell, indicates these storms are caused by cytokines released by cells that line blood vessels and lymphatic tissue in the lungs.

"Most people who have been focusing on viral infection have been focusing on the cells lining the air side of the lungs - the respiratory epithelium," says senior author Dr Hugh Rosen.

"What we've shown is that … there is amplification of the events of the cells lining the small blood vessels of the lungs that amplifies the immune response."

Using mice infected with strains of human influenza A and H1N1 swine flu, they identified that a protein on the endothelial cells called a Sphingosine-1-phosphate receptor (S1P1) is essential for flu-associated cytokine storms.

"We have the first definitive proof that cytokine storms play a significant role in acute respiratory infections like influenza, before there's been an association," says study co-author Dr Michael Oldstone.

The research showed these storms could be prevented using a small molecule to block the S1P1 receptor.

"The fact that we could block a cytokine storm specifically with a small molecule in the endothelial cells indicates the value of the cytokine storm," says Oldstone.

These findings indicate that drugs that block the SIP1 receptors could be used alongside vaccinations to prevent and treat severe illness, says Rosen.

"By blunting the amplification of cytokines, you protect from the collateral damage induced by the immune response, but the host can still fight the infection … and generate long-term memory that provides the life-long effect of immunisation."

While phase 1 trials using some of the chemical compounds identified in the research have begun in people with multiple sclerosis, a lot more work needs to be done, says Rosen.

"We know what sort of chemical compounds can be helpful in these pathways, but it's a big step in knowing that and actually having compounds that are proven to be sufficiently safe in humans," he says.

The discovery could also help identify people who are more genetically susceptible to cytokine storms, adds Rosen.

Leap forward

Professor Andrew Lloyd, director of the Inflammation and Infection Research Centre at the University of New South Wales says the research is a "big leap forward".

"It's potentially opening a whole new avenue of treatment programs for humans with a range of infective and immunological disorders," says Lloyd, who was not involved in the research.

"This group may well have identified a critical step [in the immune system pathway] that could plausibly be targeted."

But Lloyd says the results are yet to be proven in the broader scheme of mouse models and human studies.

"This is a very contrived system in mice. It's not clear that the phenomena that they are interested in will recapitulate into humans, or will have relevance to other viruses.